The invention provides a drug delivery device comprising a ring figure that is retained in the stomach for predictable and extended periods of time for releasing therapeutic or other beneficial agents.
Many orally administered drugs fail to achieve their full potential because of a number of problems including:
a. Slow and incomplete intestinal absorption. PA1 b. Existence of preferential absorption sites in the gastrointestinal tract (absorption windows). PA1 c. Short biological half-life (in particular if the therapeutic index is low).
Solutions to the delivery problems for these agents cannot be guaranteed using conventional controlled release technology since the site of drug release may be beyond the site of optimal absorption or the transit time through the absorbing portion of the gastrointestinal tract may be too short to effect an increase in the duration of action of the drug. In order to optimize the delivery of these agents to achieve maximum effectiveness (and reduce concentration-related side effects) it is desirable to obtain a drug delivery device which would be retained in the stomach for a prolonged, predictable period of time during which it would release the agent in a predetermined pattern. At the end of its period of usefulness, the device would disintegrate or otherwise alter its properties such that it would exit from the stomach and pass down the intestine.
Accordingly, it is an object of the invention to provide a means of retaining the dosage form in the stomach for an extended, predictable period of time. Thereby the duration of absorption and hence the duration of action of drugs with short biological half-lives could be extended. Likewise the bioavailability of the agents could be improved over that achieved from a conventional dosage form or conventional sustained release preparation.
Another object of the invention is to provide a mechanism whereby after a predetermined time the device will erode, disintegrate or otherwise alter its properties and pass out of the stomach and into the intestine. In addition the device should not lodge in the intestine thereby causing an obstruction.
A further object is to devise a device which will not obstruct the passage of food while the device is in the stomach or after it has passed into the intestine.
Other objects, features and advantages of the invention will be apparent to one skilled in the art from the detailed description of the invention which follows.
Immediately after consumption of food, the stomach acts as a holding tank for the solids while they are digested and broken down into small particles (1-2 mm in diameter) by the action of acid, enzymes and the physical grinding of the food particles by muscular contractions of the stomach wall. Due to the sieving action of the pyloric valve only particles of the order of 1-2 mm leave the stomach and pass into the intestine during the digestive period. Approximately two hours after digestion of a meal, the stomach passes into its interdigestive phase during which there are regular and frequent (every 11/2-2 hours) periods of intense contraction known as the interdigestive migratory myoelectric complex (IMMC). These contractions which can apply forces up to 200 cm of water (approximately 0.2 atmospheres pressure) are designed to remove any remaining ingested food from the stomach through a fully open pylorus. Clearly, then, any dosage form which is designed to remain in the stomach for an extended period (i.e., greater than a few hours) must be capable of withstanding these contractive forces to prevent it from passing from the stomach into the intestine.